The requirement of an adherent cell substratum for the growth of developing plasmacytoma cells in vivo.

Abstract

The intraperitoneal injection of pristane (2,6,10,14-tetramethylpentadecane) produces an environment conductive to primary plasmacytoma growth in as few as 3 days. After pristane injection, the total free peritoneal cell population increases from a normal value of 1.55 X 10(6) to 5.28 X 10(6) and remains at this elevated level for at least 50 days. The adherent peritoneal cell population, composed of both mononuclear cells and polymorphonuclear leukocytes, is the primary source of this increase. In the pristane-conditioned peritoneum, these cells rapidly form a chronic granuloma on the peritoneal connective tissues. Daily subcutaneous treatment of mice with 0.5 mg of hydrocortisone beginning simultaneously with pristane injection prevents the increase in the peritoneal cell population, granuloma formation, d the production of a conditoned environment. In mice treated with hydrocortisone beginning 3 days after pristane injection, however, neither the peritoneal cell increase nor the production of a conditioned environment is prevented. The intraperitoneal injection of thioglycolate medium at 4-day intervals produces an elevation of the free adherent peritoneal cell population similar to pristane, but does not produce a granuloma or a conditioned environment. The intraperitoneal transfer of thioglycolate-induced adherent peritonel cells to mice treated with pristane and hydrocortisone simultaneously restores the production of a conditioned environment. These findings indicate that the adherent peritoneal cell population is responsible for the conditioning effect, and that the establishment of a resident population of these cells is necessary to produce conditioning.

Elevated interleukin 6 is induced by prostaglandin E2 in a murine model of inflammation: possible role of cyclooxygenase-2.

“…A similar level of inhibition by indomethacin is observed when cells are treated with an acute stimulus in vitro (e.g., pAlb, LPS). Unlike corticosteroids (55,56), indomethacin does not prevent the inflammatory response to pristane (15) and has no direct effect on IL-6 gene expression. Rather, it acts by inhibiting a biochemical pathway(s) associated with the inflammation induced by pristane: prostaglandin synthesis.…”

Type I Interferon Modulates Monocyte Recruitment and Maturation in Chronic Inflammation

“…The influx of mononuclear and polymorphonuclear leukocytes to the peritoneal cavity persists for months after injection of this hydrocarbon oil. 9 The chronic inflammatory state also promotes tumorigenesis, as TMPD was found to induce plasmacytomas more than three decades ago. 10 TMPD is used to stimulate monoclonal antibody production by hybridoma cells injected i.p., an effect of chronic interleukin (IL)-6 production in response to the oil.…”

“…9 Ectopic lymphoid tissue may play a key role in the induction of lupus-like autoimmune disease (autoantibodies, glomerulonephritis, arthritis, and pulmonary vasculitis) in TMPD-treated mice. 12,13 How TMPD causes chronic inflammation is not well understood, but a pathological role of several cytokines has been suggested.…”

In vitro culture of primary plasmacytomas requires stromal cell feeder layers.

“…introduction of plastic materials (1), mineral oils (2)(3)(4), or alkanes such as pristane (2,6,10,14-tetramethylpentadecane) (5). Such treatment results in the formation of a chronic granulomatous tissue on the peritoneal surfaces (2,6,7) that is the site of the developing plasmacytoma. Treatment with antiinflammatory drugs, such as hydrocortisone and indomethacin, inhibits plasmacytoma development (7,8), suggesting a critical role for granulomatous tissue in early stages of plasmacytoma growth.…”